Monte Carlo studies of folding, dynamics, and stability in α-helices

Folding simulations of polyalanine peptides were carried out using an off-lattice Monte Carlo simulation technique. The peptide was represented as a chain of residues, each of which contains two interaction sites: one corresponding to the C a atom and the other to the side chain. A statistical potential was used to describe the interaction between these sites. The preferred conformations of the peptide chain on the energy surface, starting from several initial conditions, were searched by perturbations on its generalized coordinates with the Metropolis criterion. We observed that, at low temperatures, the effective energy was low and the helix content high. The calculated helix propagation (s) and nucleation (sigma) parameters of the Zimm-Bragg model were in reasonable agreement with the empirical data. Exploration of the energy surface of the alanine-based peptides (AAQAA)(3) and AAAAA( AAARA)(3)A demonstrated that their behavior is similar to that of polyalanine, in regard to their effective energy, helix content, and the temperature-dependence of their helicity. In contrast, stable secondary structures were not observed for (Gly)(20) at similar temperatures, which is consistent with the nonfolder nature of this peptide. The fluctuations in the slowest dynamics mode, which describe the elastic behavior of the chain, showed that as the temperature decreases, the polyalanine peptides become stiffer and retain conformations with higher helix content. Clustering of conformations during the folding phase implied that polyalanine folds into a helix through fewer numbers of intermediate conformations as the temperature decreases.